Conventional methods of contraception include the use of mechanical or chemical barriers to fertilization, administration of hormones, or the use of mechanical means to prevent implantation of a fertilized ovum. Typically, these methods have serious drawbacks, including practical inconvenience, incomplete effectiveness and various undesirable side effects. Mechanical means of contraception may cause infection and are often not sufficiently effective. The oral administration of hormones, commonly referred to as "the pill," has been linked to many physiological problems, including various forms of cancer.
In view of the disadvantages of such treatments, efforts have been directed to making use of the body's immune system to prevent conception. For example, immunization against hormones such as follicle stimulating hormone (FSH) or human chorionic gonadotropin hormone (HCG) for the purpose of contraception has been previously reported [U.S. Pat. No. 4,526,716]. However, these methods are also characterized by various side effects.
The zona pellucida ("ZP"), is a glycoprotein matrix encasing mammalian oocytes which plays an important role in the reproductive process. Its primary functions include the binding of sperm through its sperm-binding receptors, the prevention of polyspermy following fertilization, and the protection of the zygote until ZP shedding immediately prior to implantation. One method of reproduction control comprises denuding a blastocyte by removing its ZP [U.S. Pat. No. 4,248,864].
Purified ZP is an efficient immunogen, evoking high levels of specific antibodies when injected into species other than the one from which the ZP preparation was derived. Methods of contraception have been developed which rely on the fact that, when females are immunized with ZP, the elicited antibodies to ZP are capable of preventing pregnancy [U.S. Pat. No. 3,992,520].
The effectiveness of treatments involving the use of purified ZP, however, has been limited by a variety of factors, including the need for the large amount of purified protein necessary to elicit the immune response. The purification of ZP, which is time-consuming and expensive, has made such contraceptive methods which require large amounts of pure ZP impractical.
In addition, immunizing with purified whole ZP, or any of its major subunits, elicits heterogeneous antibody populations directed against the numerous antigenic determinants expressed by ZP. Many of the antibodies thus elicited may be irrelevant to effective contraception. Studies have shown that certain monoclonal anti-ZP antibodies are not contraceptive [D. W. Drell and B. S. Dunbar, "Monoclonal Antibodies To Rabbit And Pig Zona Pellucide Distinguish Species--Specific And Shared Antigenic Determinants," Biology Of Reproduction, 30 p. 445 (1984)]. This approach allows for no control over the specificity of the anti-ZP antibodies thus elicited, and may be not only wasteful but also harmful. It has been demonstrated in experiments with rabbits that immmunization with whole ZP can result in serious negative side effects, including alterations in follicular cell differentiation accompanied by abnormally elevated serum gonadotropin levels [J. M. Skinner et al., "Immunization With Zona Pellucida Proteins Results In Abnormal Ovarian Follicular Differentiation An Inhibition Of Gonadotropin-Induced Steroid Secretion," Endocrinology 115, p. 2418 (1984)].